This invention relates to compositions and methods capable of detecting cancer cells or malignant tumors in humans. More particularly, this invention relates to compositions radio-labeled with Technetium-99m which, when administered to a human will accumulate at cells producing hCG, hCG-like material, and a compound similar to and/or identical to the beta-chain of chorionic gonadotropin, or mixtures thereof.
The use of compositions which emit radiation at levels which can be detected after administration to the human body are well known. These compositions are utilized to visualize and/or monitor functioning of various parts of the body or are utilized diagnostically to determine the presence or absence of particular antigens, antibodies, hormones or the like. In one particular aspect of the prior art, radiolabeled antibodies are utilized to detect tumors having associated therewith carcinoembryonic antigen. As disclosed in U.S. Pat. Nos. 3,663,684, 3,867,363 and 3,927,193, I.sup.131 or I.sup.125 labeled antibodies to carcinoembryonic antigen are utilized to detect tumors which produce or are associated with carcinoembryonic antigen. It is also well known that protein molecules can be tagged with Technetium-99m in order to form diagnostic agents. It has also been proposed to tag the antibody of the beta chain of human chorionic gonadotropin with peroxidase (McManus et al, Cancer Research, 36, pp. 2367-3481, September, 1976) in order to localize the antigen in malignant tumors.
Recently, it has been found that neoplastic tissues produce chorionic gonadotropin, chorionic gonadotropin-like material, and a compound similar to and/or identical to the .beta.-chain of chorionic gonadotropin (hCG-.beta. subunit) or mixtures thereof, specifically to the degree where it is considered more cancer specific than either carcinoembryonic antigen (CEA) or alphafetoprotein (AFP). The positive identification of chorionic gonadotropin in a heterogenous group of cancer cells and its absence in non-cancer cells in tissue culture has suggested that:
(a) this is a unique trophoblastic-like sialoglycoprotein which is synthesized de-novo by the malignant cells;
(b) since CG and/or CG-like glycoprotein has been observed only in the trophoblast and human spermatozoa, its production by the cancer cells can only be explained by an expression of the information which opens the mechanism(s) for its biosynthesis, either by derepression or by an activation of the genetic control;
(c) the compound is a common antigen (common denominator) of every cell with oncogenic properties.
It is also believed that chorionic gonadotropin is one of the factors involved in maternal immunosuppression. In support of this belief, it has been shown that chorionic gonadotropin has been shown to block maternal lymphocyte cytotoxicity, maternal lymphocyte mitosis and to inhibit phytohemagglutin-induced and mixed lymphocyte blast transformation.
While peroxidase-labeled or fluorescein-labeled anti-hCG-beta or anti-hCG are effective for identifying and localizing malignant cells, these labeled compositions are undesirable for in-vivo use because they do not allow for visualization by any available detection system and are otherwise undesirable for widespread use because they are simply an invitro immunohistochemical technique requiring light or electron microscopy of biopsy samples for positive identification.
Accordingly, it would be highly desirable to provide a labeled anti-hCG-beta or anti-hCG which can be utilized invivo and which overcomes the disadvantages of the prior art compositions.